PT Unknown
AU Hildebrandt, C
TI Improving die filling in pharmaceutical tableting by experimental and numerical means
PY 2018
PU Christian-Albrechts-Universität zu Kiel
WP https://macau.uni-kiel.de/receive/diss_mods_00024364
LA en
DE Pharmaceutical Tableting; Die Filling; Discrete Element Method; Pharmazeutische Tablettierung; Matrizenfüllung; Diskrete Element Methode
AB Pharmaceutical tableting consists of three distinct stages: die filling, powder compaction, and tablet ejection. The first step is crucial with respect to the patient's safety as it defines the content and content uniformity of the active pharmaceutical ingredient(s). 
In this work, different experimental and numerical methods were developed to improve process understanding in die filling as in reality, nontransparent gravity or force feeders impede a detailed examination of the powder transfer into the dies. 
In the first step, a transparent model die filling system was developed to visualize powder discharge into the die by high speed camera imaging and to discern powder flow patterns. Several mathematical correlations were established to estimate the flowability for new materials in die filling and thus to quantify the effect of particle size enlargement on powder flowability improvement.
The Discrete Element Method (DEM), which tracks each individual particle and thus provides a high level of detail in complex powder handling / transporting systems, was utilized to understand die filling in different gravity and force feeders. Thus powder flow patterns through the feeding systems could be discerned and the underlying size segregation mechanisms and dead / high shear zones identified. Those could be related to geometrical properties of the feeder types. First hints to critical material properties (powder cohesivity and particle-wall coefficient of friction) and critical process conditions (turret speed and paddle wheel speed) on critical quality attributes (tablet mass, tablet mass variation, and content uniformity) were provided. 
The application of different means, such as custom-designed instruments, statistical tools, and DEM, enabled a detailed understanding of powder flow in the tableting machine and its influence on tablet quality. Different levers for process and formulation optimization were presented and could aid pharmaceutical development in the context of the Quality by Design approach.
PI Kiel
ER